Cancer Cell and Gene Therapy (CCGT) Program PROJECT SUMMARY The goals of the Cancer Cell and Gene Therapy (CCGT) Program are to incorporate advances in cellular and gene therapy into the treatment of cancer. The Cancer Center Program is a sub-component of the Center for Cell and Gene Therapy and has 20 research members and 5 clinical members from multiple Departments at Baylor, including Medicine, Pediatrics, Surgery, Pathology and Immunology, Molecular and Cell Biology, Neuroscience and Molecular and Human Genetics. The program received a total of $5,633,954 in support from the NCI last year and overall received $18,611,435 in peer-reviewed funding and $21,586,829 in total funding. In the last five years, members of the program published 412 cancer related manuscripts in peer-reviewed journals, of which 49% represented intraprogrammatic collaborations and 26% interprogrammatic while 39% included external collaborators. Our research focuses on three themes: normal and malignant stem cells, adoptive immunotherapy of cancer, and improving outcomes of stem cell transplantation for cancer. CCGT has basic, translational and clinical research components. Our basic investigators work on understanding the mechanisms by which normal and malignant stem cell growth is controlled, and on the molecular and cellular interactions involved in the development of tumor vasculature and stroma. These researchers are also identifying new targets for immunotherapy, and optimizing presentation of weak tumor antigens to the immune system. Our translational investigators are moving cell- and gene-based therapies from the bench to the bedside in a series of small-scale iterative laboratory-clinical-laboratory protocols, and are also developing pivotal trials. We have a decade-long history of successful and timely implementation of clinical translational projects in gene and cellular therapy, and we have the resources to supply and test all the clinical reagents required, since our center is one of five national NHLBI-funded Production Assistance for Cellular Therapy centers. Major accomplishments include the demonstration of activity of virus specific cytotoxic T lymphocytes in virus-associated cancers (resulting in licensure of the approach to three companies for late phase trials) and studies showing the anti-tumor activity of genetically modified T cells in subjects with neuroblastoma and lymphoma. Our clinical researchers run the adult and (in collaboration with the Pediatric Cancer program) pediatric hemopoietic stem cell transplant programs and are extending the applicability of transplantation for malignancy by using post transplant immunotherapy to augment graft-versus-tumor activity and reconstitute anti-viral immunity.